Coronary artery disease (CAD) is the leading cause of death and disability in the United States and other industrialized nations. Family history is a significant cardiovascular risk factor that has been underutilized in standard risk assessment methods for CAD and in guidelines for preventive interventions. Using existing data available in the NHLBI-funded Multi-Ethnic Study of Atherosclerosis (MESA) and an existing method for comprehensive familial risk assessment for clinical CAD developed for the Centers for Disease Control and Prevention family history tool, we will develop a familial risk assessment method for subclinical CAD that will assign a level of familial risk (e.g., weak, moderate or strong) to each MESA participant. We will evaluate the ability of this method to stratify an individual's risk for subclinical CAD compared to a standard method that uses other traditional risk factors (i.e., the Framingham Risk Score). We will determine whether traditional or emerging risk factors, such as homocysteine and C-reactive protein, aggregate in individuals with increased familial risk, and we will describe the impact of familial risk assessment for subclinical CAD on current guidelines for lipid-lowering treatment. These results may inform clinical decision-making regarding the role of family history in overall risk assessment for CAD, and the role of increased familial risk as an indication for screening for subclinical CAD or testing for emerging cardiovascular risk factors. In addition, the incremental value of comprehensive familial risk assessment in decision-making regarding lipid-lowering treatment with diet or drugs for primary prevention of CAD will be analyzed. [unreadable] [unreadable] [unreadable]